Fig. 1.

Representation of a heavy-chain antibody (HcAb) and its antigen binding fragment, called nanobody. A. In contrast to a monoclonal antibody (mAb), which comprises two heavy and two light chains, an HcAb only contains heavy chains. As HcAbs also lack one constant domain, the antigen binding region only consists of a single fragment, called a nanobody. The tail region of the antibodies forms the Fc part and is able to trigger the immune system. B. Schematic representation (left) and conformation (right) of the nanobody entity, composed of framework regions (FR1–4) alternated with three complementary determining regions (CDR1–3). Mutations in FR2 (stars) render the structure more hydrophilic as compared to conventional antibody fragments. Moreover, the CDR3 loop is extended and enables recognition of hidden or buried epitopes.